The goal of this proposal is to develop novel immunological approaches for controlling IgE-mediated allergic diseases. IgE binds its high-affinity receptor on mast cells (FceRI) and this interaction plays a central role in allergic disorders. Small molecule inhibitors targeting the IgE-FceRI interaction could prove effective anti-allergy therapeutics. In preliminary studies, a peptide analog of FceRI was shown to significantly inhibit IgE-FceRI binding and IgE-mediated responses in vitro. To further improve the clinical potential of this peptide, various synthetic modification have been made to increase its potency and enzymatic stability. In addition, a computer-assisted database screening method has been developed to identify non-peptide inhibitors of IgE function. These studies will be extended to further characterize the role of the IgE-FceRI interaction in mediating allergic responses and to develop a new class of potent and stable IgE inhibitors as potential therapeutic agents.